Karsaj I, Humphrey J D
Faculty of Mechanical Engineering and Naval Architecture, University of Zagreb, Zagreb, Croatia.
Biorheology. 2009;46(6):509-27. doi: 10.3233/BIR-2009-0556.
Quantifying mechanical properties of blood clots is fundamental to understanding many aspects of cardiovascular disease and its treatment. Nevertheless, there has been little attention to quantifying the evolving composition, structure and properties when a clot transforms from an initial fibrin-based mesh to a predominantly collagenous mass. Although more data are needed to formulate a complete mathematical model of the evolution of clot properties, we propose a general constrained mixture model based on diverse data available from in vitro tests on fibrinogenesis, the stiffness of fibrin gels, and fibrinolysis as well as histological and mechanical data from clots retrieved from patients at surgery or autopsy. In particular, albeit resulting from complex kinetics involving many clotting factors, we show that the rapid (minutes) in vitro production of fibrin from fibrinogen can be modeled well by an Avrami-type relation and similarly that the fast (tens of minutes) in vitro degradation of fibrin in response to different concentrations of plasmin can be captured via a single "master function" parameterized by appropriate half-times that can be inferred from laboratory or clinical data. Accounting simultaneously for the production and removal of fibrin as well as chemo-mechano-stimulated production of fibrillar collagens yields predictions of changing mass fractions and bulk mechanical properties that correspond well to experimentally available data. Constrained mixture models thus hold considerable promise for modeling the biomechanics of clot evolution and can guide the design and interpretation of needed experiments and stress analyses.
量化血凝块的力学特性对于理解心血管疾病的诸多方面及其治疗至关重要。然而，当血凝块从最初基于纤维蛋白的网状结构转变为主要由胶原质构成的团块时，对于量化其不断演变的组成、结构和特性却鲜有关注。尽管需要更多数据来构建一个完整的血凝块特性演变数学模型，但我们基于来自纤维蛋白生成的体外测试、纤维蛋白凝胶的硬度、纤维蛋白溶解以及从手术或尸检患者身上获取的血凝块的组织学和力学数据等多种数据，提出了一个通用的约束混合模型。特别是，尽管纤维蛋白原形成纤维蛋白涉及许多凝血因子的复杂动力学过程，但我们表明，纤维蛋白原在体外快速（数分钟）生成纤维蛋白的过程可以通过阿弗拉米型关系很好地建模，同样，在不同浓度纤溶酶作用下纤维蛋白在体外快速（数十分钟）降解的过程可以通过一个由适当半衰期参数化的单一“主函数”来捕捉，这些半衰期可以从实验室或临床数据中推断出来。同时考虑纤维蛋白的产生和去除以及化学 - 机械刺激下纤维状胶原蛋白的产生，能够得出与实验可用数据相当吻合的质量分数变化和整体力学特性预测。因此，约束混合模型在模拟血凝块演变的生物力学方面具有很大的潜力，并可以指导所需实验的设计和解释以及应力分析。
